TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15064	45415;45416;45417	chr2:178621634;178621633;178621632	chr2:179486361;179486360;179486359
N2AB	13423	40492;40493;40494	chr2:178621634;178621633;178621632	chr2:179486361;179486360;179486359
N2A	12496	37711;37712;37713	chr2:178621634;178621633;178621632	chr2:179486361;179486360;179486359
N2B	5999	18220;18221;18222	chr2:178621634;178621633;178621632	chr2:179486361;179486360;179486359
Novex-1	6124	18595;18596;18597	chr2:178621634;178621633;178621632	chr2:179486361;179486360;179486359
Novex-2	6191	18796;18797;18798	chr2:178621634;178621633;178621632	chr2:179486361;179486360;179486359
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-102
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.1479
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Y/F	rs1194753380	None	0.002	N	0.201	0.355	0.444305618086	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/F	rs1194753380	None	0.002	N	0.201	0.355	0.444305618086	gnomAD-4.0.0	6.58423E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47301E-05	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Y/A	0.7594	likely_pathogenic	0.7833	pathogenic	-3.174	Highly Destabilizing	0.842	D	0.577	neutral	None	None	None	None	N
Y/C	0.2324	likely_benign	0.2266	benign	-1.65	Destabilizing	0.997	D	0.58	neutral	D	0.708143444	None	None	N
Y/D	0.6677	likely_pathogenic	0.6514	pathogenic	-2.731	Highly Destabilizing	0.989	D	0.637	neutral	D	0.607915086	None	None	N
Y/E	0.7802	likely_pathogenic	0.7854	pathogenic	-2.614	Highly Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
Y/F	0.0876	likely_benign	0.0925	benign	-1.389	Destabilizing	0.002	N	0.201	neutral	N	0.469116207	None	None	N
Y/G	0.6479	likely_pathogenic	0.6813	pathogenic	-3.505	Highly Destabilizing	0.915	D	0.625	neutral	None	None	None	None	N
Y/H	0.2112	likely_benign	0.2129	benign	-1.787	Destabilizing	0.989	D	0.582	neutral	D	0.545126743	None	None	N
Y/I	0.6236	likely_pathogenic	0.6608	pathogenic	-2.106	Highly Destabilizing	0.728	D	0.558	neutral	None	None	None	None	N
Y/K	0.7151	likely_pathogenic	0.7391	pathogenic	-1.838	Destabilizing	0.974	D	0.599	neutral	None	None	None	None	N
Y/L	0.5472	ambiguous	0.589	pathogenic	-2.106	Highly Destabilizing	0.016	N	0.287	neutral	None	None	None	None	N
Y/M	0.6589	likely_pathogenic	0.6972	pathogenic	-1.744	Destabilizing	0.949	D	0.58	neutral	None	None	None	None	N
Y/N	0.2964	likely_benign	0.3031	benign	-2.248	Highly Destabilizing	0.989	D	0.597	neutral	D	0.608126503	None	None	N
Y/P	0.9927	likely_pathogenic	0.9934	pathogenic	-2.468	Highly Destabilizing	0.991	D	0.645	neutral	None	None	None	None	N
Y/Q	0.5842	likely_pathogenic	0.6077	pathogenic	-2.242	Highly Destabilizing	0.991	D	0.591	neutral	None	None	None	None	N
Y/R	0.5507	ambiguous	0.5682	pathogenic	-1.221	Destabilizing	0.974	D	0.598	neutral	None	None	None	None	N
Y/S	0.4128	ambiguous	0.4195	ambiguous	-2.706	Highly Destabilizing	0.891	D	0.594	neutral	D	0.522531544	None	None	N
Y/T	0.6655	likely_pathogenic	0.696	pathogenic	-2.495	Highly Destabilizing	0.915	D	0.594	neutral	None	None	None	None	N
Y/V	0.5535	ambiguous	0.5923	pathogenic	-2.468	Highly Destabilizing	0.728	D	0.566	neutral	None	None	None	None	N
Y/W	0.4384	ambiguous	0.4663	ambiguous	-0.766	Destabilizing	0.991	D	0.573	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.